Mol is a leukocyte surface glycoprotein heterodimer (alpha subunit 155 Kd, beta subunit 94 Kd) that is closely associated or identical with a receptor for C3bi, a major fragment of the third component of complement (C3). It is present on monocytes, granulocytes and null cells. The beta subunit of Mol is shared by another leukocyte glycoprotein associated with lymphocyte killing activity named LFA1 (alpha subunit 177 Kd). We have recently described a patient with recurrent bacterial infections who is deficient in Mol and LFAl. Subsequently seven more patients in six families were discovered suggesting that this newly discovered disorder is not uncommon. The inherited basis of this disorder is further indicated by occurrence of more than one patient in one family and by recognition that one or both parents may be carriers. We propose to determine the molecular basis of human Mol/LFAl deficiency and the factors involved in surface expression of this family of molecules. We plan to study biosynthesis, postsynthetic processing, kinetics of insertion and turnover of these two membrane proteins in primary human monocyte cultures from normal individuals, patients with Mol/LFAl deficiency and their parents. Cell free translation and biosynthesis in Xenopus oocytes of mRNA from normals and Mol deficient patients will be studied. We will purify the two noncovalently linked chains of Mol and obtain limited amino acid sequence of cyanogen bromide fragments to synthesize specific oligonucleotide probes. These probes will be used to isolate specific cDNA sequences from a human monocyte cDNA library. cDNA clones will be characterized and used to localize the gene(s) for Mol in normals and deficient patients. The results of these studies should be instrumental in defining the molecular basis of this newly discovered disorder in man and should provide insight into the structure and function of a new family of leukocyte surface glycoproteins in normal cells.